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Background and Purpose: Spasticity is a common disorder and a major cause of long-term disability in patients with multiple sclerosis (MS). Our aim was to evaluate whether a recently developed repetitive transcranial magnetic stimulation protocol, the intermittent theta burst stimulation (iTBS) is effective in modulating lower limb spasticity in MS patients., Methods: Twenty MS patients were pseudorandomized to undergo a 2-week daily sessions of real or sham iTBS protocol. The H/M amplitude ratio of the Soleus H reflex, a reliable neurophysiological index of spinal excitability and the Modified Ashworth Scale (MAS) for spasticity were evaluated by blinded raters before and after the stimulation protocols., Results: Patients receiving real iTBS showed a significant reduction of H/M amplitude ratio and MAS scores 1 week after the stimulation and persisting up to 2 weeks after the end of stimulation protocol. There were no significant effects for sham stimulation., Conclusions: These results show that iTBS, a safe, non-invasive, well-tolerated and feasible protocol, is a promising tool for the treatment of spasticity in MS.

In the present in vitro electrophysiological study, the acute effects of the cerebrospinal fluid (CSF) from multiple sclerosis (MS) and control subjects were measured on the axonal conduction of rat optic nerve, a central tract that is commonly affected in MS. Optic nerve compound action potential (CAP) amplitude was insensitive to the application of CSF obtained from the whole population of non-MS patients and from seven of 15 MS CSF. In the remaining eight MS cases, conversely, a time-dependent depression of CAP amplitude was observed. The reversible blockade of ion channels by soluble substances might account, at least in part, for the transient symptoms often seen in MS patients.

Sodium cyanate, which in its tautomeric acidic form, isocyanic acid, acts as a protein carbamylating reagent, has been previously shown to inhibit selectively both DNA and protein synthesis in a variety of solid tumors. We have now compared its effects on protein synthesis in normal colonic epithelium and in colon tumors induced by the administration of 1,2-dimethylhydrazine to rats. The incorporation of 3H-amino acids into cytoplasmic and nuclear protein fractions was suppressed to a much greater extent in the tumor tissue than in colonic epithelial tissue surrounding the tumors of cyanate-treated rats. Despite its effect on tumor protein synthesis in whole animals, cyanate had little or no effect on cultured cells (HT-29) derived from a human adenocarcinoma of the colon, nor on other malignant cell lines such as HeLa S3 cells, chick fibroblasts transformed by the Rous sarcoma virus, mouse Ehrlich ascites tumor cells, or rat Novikoff hepatoma cells. However, the administration of cyanate i.p. does suppress amino acid incorporation by Novikoff hepatoma cells in the peritoneal cavity of rats. The implication that the mechanism of cyanate inhibition of protein synthesis in tumors may require its in vivo metabolism or utilization to produce a postsynthetic modification of circulatory factors is discussed.

The complement of nuclear non-histone proteins in epithelial cells of the colon is progressively altered during the course of carcinogenesis induced by 1, 2-dimethylhydrazine, until finally the nuclear proteins of tumor cells are easily distinguishable from those of the surrounding normal tissue. These changes in nuclear protein compostion reflect earlier differences in the rates of synthesis of individual protein species. Radioisotopic double-labeling experiments show that the synthesis of nuclear proteins of molecular weights 44,000 and 62,000 is selectively accelerated within 4 weeks after administration of the carcinogen, long before any morphological indications of malignancy appear.

The properties of two classes of nonhistone nuclear proteins (NHNP) whose appearance has been correlated with the process of carcinogenesis in the colonic epithelium of rats given 1,2-dimethylhydrazine (DMH) have been investigated. NHNP isolated from adenocarcinomas of the colon were tested for their binding to homologous DNA. The tumor-specific protein class TNP1 (molecular weight ca. 44,000) shows high affinity for DNA while the second class of tumor-specific proteins (TNP2; molecular weight ca. 62,000) does not bind to DNA. When tumor chromatin is subjected to a limited digestion with DNAse I under conditions that are known to preferentially digest active genes, the TNP1 proteins are selectively released, suggesting that this protein fraction is associated with the actively transcribing portions of the genome. The complexity of both tumor-specific protein classes has also been analyzed by two-dimensional gel electrophoresis. This method reveals a high degree of complexity both in TNP1 and TNP2. Protein classes similar to TNP1 and TNP2 that are also found in human colonic adenocarcinomas are not detectable in polyps from familial polyposis-affected patients at times when no sign of malignancy has yet appeared.